With millions of single nucleotide polymorphisms (SNPs) identified, there is now a great need for prioritizing potential functional SNPs that are most likely to affect phenotypic functions and ultimately contribute to disease development. This proposal will explore the application of available bioinformatic methods in functional SNP selection by focusing on genes responsible for environmental responses. Validity of these approaches will be assessed by literature search and empirical confirmations. Specifically, the aims of this proposal are: 1) To identify SNPs with potential functional importance in approximately 700 environmentally responsive genes using SNPs collected from public SNP databases and screened by available bioinformatic tools. A functional SNP database will be constructed. 2).To survey previous publications examining SNP functionality and their roles in cancer case-control studies. Results will be integrated with the SNP database. 3) To determine to what extent the predictive value of SNP functionality is mirrored in findings from molecular epidemiologic studies. Since most of these environmentally responsive genes are involved in cancer development, our hypothesis is that SNPs predicted to have significant impact on protein function are more likely to be associated with cancer risk in terms of odds ratios detected in previous case-control studies. Functional SNPs generated from this interdisciplinary approach will become publicly available. Findings from this study will enhance the use of SNPs in future phenotypic studies and molecular epidemiologic approaches to address questions related to gene-environment interaction in disease risk estimate.